Clinical Trials Program Project Summary/Abstract The overall goal of the proposal is to advance prevention interventions for HPV-associated cancers occurring among men and women living with HIV in Latin America and the Caribbean (LAC). We are focusing on prevention of two HPV-associated cancers, oropharyngeal cancer and cervical cancer. Both cancers are significantly elevated among individuals living with HIV compared to HIV negative populations and present prevention, screening, and treatment challenges requiring new solutions. To address these significant public health concerns, we will perform the following clinical trials: 1. Investigate immunoprevention of persistent oral HPV infection, a surrogate for prevention of HPV- associated OPC, by conducting a double-blind, randomized, placebo-controlled trial of the 9-valent HPV vaccine among men living with HIV in Brazil, Mexico and Puerto Rico 2. Evaluate and optimize primary HPV screening with triage to HPV/host DNA methylation for cervical cancer screening among women living with HIV 3. Evaluate non-surgical approaches for treating HPV-related cervical pre-cancer by evaluating the safety, immunogenicity and preliminary efficacy of a novel HPV therapeutic vaccine, PDS0101, in women living with HIV diagnosed with cervical HSIL